The use of tacrolimus for recurrent lupus enteritis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Patients with lupus enteritis sometimes experience recurrence. In such cases, the addition of cyclophosphamide to the treatment regimen is recommended. However, an appropriate treatment has not been established in cases where cyclophosphamide failed to prevent the disease.</p> <p>Case presentation</p> <p>An 18-year-old Japanese woman was admitted for a recurrence of lupus enteritis. One year before admission she was treated for lupus enteritis with high-dose corticosteroid together with intravenous cyclophosphamide pulse therapy. Upon admission, she was administered again with high-dose corticosteroid and her abdominal pain rapidly subsided. Tacrolimus was later used as an immunosuppressive agent and a complete remission has been maintained.</p> <p>Conclusion</p> <p>Tacrolimus can be a useful agent for recurrent lupus enteritis that is resistant to conventional therapy.</p

SLE peripheral blood B cell, T cell and myeloid cell transcriptomes display unique profiles and each subset contributes to the interferon signature.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is characterized by defective immune tolerance combined with immune cell hyperactivity resulting in the production of pathogenic autoantibodies. Previous gene expression studies employing whole blood or peripheral blood mononuclear cells (PBMC) have demonstrated that a majority of patients with active disease have increased expression of type I interferon (IFN) inducible transcripts known as the IFN signature. The goal of the current study was to assess the gene expression profiles of isolated leukocyte subsets obtained from SLE patients. Subsets including CD19(+) B lymphocytes, CD3(+)CD4(+) T lymphocytes and CD33(+) myeloid cells were simultaneously sorted from PBMC. The SLE transcriptomes were assessed for differentially expressed genes as compared to healthy controls. SLE CD33(+) myeloid cells exhibited the greatest number of differentially expressed genes at 208 transcripts, SLE B cells expressed 174 transcripts and SLE CD3(+)CD4(+) T cells expressed 92 transcripts. Only 4.4% (21) of the 474 total transcripts, many associated with the IFN signature, were shared by all three subsets. Transcriptional profiles translated into increased protein expression for CD38, CD63, CD107a and CD169. Moreover, these studies demonstrated that both SLE lymphoid and myeloid subsets expressed elevated transcripts for cytosolic RNA and DNA sensors and downstream effectors mediating IFN and cytokine production. Prolonged upregulation of nucleic acid sensing pathways could modulate immune effector functions and initiate or contribute to the systemic inflammation observed in SLE

SLE B cell transcriptomes.

<p>Hierarchical cluster dendrogram of expressed genes that differed significantly between peripheral blood CD19+ B cells isolated from SLE patients and healthy controls (HC). The SLE samples are ordered by increasing SLEDAI score. The bars to the left indicate expressed gene clusters. Color changes indicate the expression level relative to the average (log₂ scale). Red is increased expression, yellow is unchanged and blue is decreased expression. Indicated on the right are fold change in inactive SLE compared to HC (InAct FC), active SLE compared to HC (Act FC) and active SLE compared to inactive SLE (Act/IA FC). Select transcripts are identified for each cluster in boxes (right). For the entire list of transcripts in order as they appear on the dendrogram see supplementary <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067003#pone.0067003.s007" target="_blank">Table S1</a>.</p

Confirmation of Myeloid Array Results by CD169 Protein Expression

<p>. The high expression of CD169 (<i>SIGLEC1</i>) by myeloid cells in the arrays was confirmed by analysis of CD33⁺CD14⁺ myeloid cells in a second cohort. (A) CD14⁺ myeloid cells were gated for CD16^dim and CD16^bright myeloid cells. (B) Histograms of CD169 expression on classical (CD14⁺CD16^dim) and nonclassical (CD14⁺CD16⁺) myeloid cells. (C) Frequency of CD169⁺ cells in the classical (CD14⁺CD16^dim) myeloid subset comparing HC to SLE patients. (D) Frequency of CD169⁺ cells in the nonclassical (CD14⁺CD16⁺) myeloid subset comparing HC to SLE patients.</p

SLE Myeloid cell transcriptomes.

<p>Hierarchical cluster dendrogram of expressed genes that differed significantly between sorted peripheral blood CD33+ myeloid cells isolated from SLE patients and healthy controls (HC) as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067003#pone-0067003-g001" target="_blank">figure 1</a>. Also indicated on the right are differentially expressed genes from the B cell compartment of SLE (B FC) or the T cell compartment of SLE (T FC) that were shared with myeloid cells. Select transcripts are identified for each cluster in boxes (right). For the entire list of transcripts ordered by clusters from the dendrogram see supplementary <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067003#pone.0067003.s009" target="_blank">Table S3</a>.</p

SLE Subsets Up-regulate Unique Transcriptional Profiles.

<p>A Venn diagram demonstrating shared and unique differentially expressed transcripts of SLE myeloid cells, B cells and T cells. Of the 474 combined transcripts only 4.4% (21) were shared by all three subsets, whereas 69% (329) of the transcripts were unique to a particular subset at the threshold set for the described primary analysis.</p